Agonist-independent inactivation and agonist-induced desensitization of the G protein-activated K + channel (GIRK) in Xenopus oocytes

1998 ◽  
Vol 436 (1) ◽  
pp. 56-68 ◽  
Author(s):  
Dmitry Vorobiov ◽  
G. Levin ◽  
Ilana Lotan ◽  
N. Dascal
Keyword(s):  
G Protein ◽  
Xenopus Oocytes ◽  
K Channel

scholarly journals Positive and Negative Coupling of the Metabotropic Glutamate Receptors to a G Protein–activated K+ Channel, GIRK, in Xenopus Oocytes

1997 ◽  
Vol 109 (4) ◽  
pp. 477-490 ◽  
Author(s):  
Dahlia Sharon ◽  
Dmitry Vorobiov ◽  
Nathan Dascal
Keyword(s):  
Protein Kinase ◽  
Glutamate Receptors ◽  
G Protein ◽  
G Proteins ◽  
Metabotropic Glutamate Receptors ◽  
Xenopus Oocytes ◽  
K Channel ◽  
Metabotropic Glutamate ◽  
Girk Channel ◽  
The Brain

Metabotropic glutamate receptors (mGluRs) control intracellular signaling cascades through activation of G proteins. The inwardly rectifying K+ channel, GIRK, is activated by the βγ subunits of Gi proteins and is widely expressed in the brain. We investigated whether an interaction between mGluRs and GIRK is possible, using Xenopus oocytes expressing mGluRs and a cardiac/brain subunit of GIRK, GIRK1, with or without another brain subunit, GIRK2. mGluRs known to inhibit adenylyl cyclase (types 2, 3, 4, 6, and 7) activated the GIRK channel. The strongest response was observed with mGluR2; it was inhibited by pertussis toxin (PTX). This is consistent with the activation of GIRK by Gi/Go-coupled receptors. In contrast, mGluR1a and mGluR5 receptors known to activate phospholipase C, presumably via G proteins of the Gq class, inhibited the channel's activity. The inhibition was preceded by an initial weak activation, which was more prominent at higher levels of mGluR1a expression. The inhibition of GIRK activity by mGluR1a was suppressed by a broad-specificity protein kinase inhibitor, staurosporine, and by a specific protein kinase C (PKC) inhibitor, bis-indolylmaleimide, but not by PTX, Ca2+ chelation, or calphostin C. Thus, mGluR1a inhibits the GIRK channel primarily via a pathway involving activation of a PTX-insensitive G protein and, eventually, of a subtype of PKC, possibly PKC-μ. In contrast, the initial activation of GIRK1 caused by mGluR1a was suppressed by PTX but not by the protein kinase inhibitors. Thus, this activation probably results from a promiscuous coupling of mGluR1a to a Gi/Go protein. The observed modulations may be involved in the mGluRs' effects on neuronal excitability in the brain. Inhibition of GIRK by phospholipase C–activating mGluRs bears upon the problem of specificity of G protein (GIRK interaction) helping to explain why receptors coupled to Gq are inefficient in activating GIRK.

Muscarine-gated K+ channel: subunit stoichiometry and structural domains essential for G protein stimulation

1996 ◽  
Vol 271 (1) ◽  
pp. H379-H385 ◽  
Author(s):  
S. J. Tucker ◽  
M. Pessia ◽  
J. P. Adelman
Keyword(s):  
G Protein ◽  
Xenopus Oocytes ◽  
K Channel ◽  
Channel Activity ◽  
Atrial Myocytes ◽  
Structural Domains ◽  
Maximal Stimulation ◽  
Subunit Stoichiometry ◽  
K Current ◽  
Inwardly Rectifying

Coexpression in Xenopus oocytes of the cloned cardiac inward rectifier subunits Kir 3.1 and Kir 3.4 results in G protein-stimulated channel activity closely resembling the muscarinic channel underlying the inwardly rectifying K+ current in atrial myocytes. To determine the stoichiometry and relative subunit positions within the channel, Kir 3.1 and Kir 3.4 were coexpressed in varying ratios with cloned G beta 1 gamma 2 subunits and also as tandemly linked tetramers with different relative subunit positions. The results reveal that the most efficient channel comprises two subunits of each type in an alternating array within the tetramer. To localize regions important for subunit coassembly and G protein sensitivity, chimeric subunits containing domains from either Kir 3.1, Kir 3.4, or the G protein-insensitive subunit Kir 4.1 were expressed. The results demonstrate that the transmembrane domains dictate the potentiation of the coassembled channels and that, although the NH4- or COOH-termini of both subunits alone can confer G protein sensitivity, both termini are required for maximal stimulation by G beta 1 gamma 2.

scholarly journals A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes.

1995 ◽  
Vol 105 (3) ◽  
pp. 421-439 ◽  
Author(s):  
N F Lim ◽  
N Dascal ◽  
C Labarca ◽  
N Davidson ◽  
H A Lester
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Xenopus Oocytes ◽  
K Channel ◽  
Intracellular Camp ◽  
Heterotrimeric G Proteins ◽  
M2 Muscarinic Receptor ◽  
Gamma Subunits ◽  
Beta 2 ◽  
Inwardly Rectifying

In many tissues, inwardly rectifying K channels are coupled to seven-helix receptors via the Gi/Go family of heterotrimeric G proteins. This activation proceeds at least partially via G beta gamma subunits. These experiments test the hypothesis that G beta gamma subunits activate the channel even if released from other classes of heterotrimeric G proteins. The G protein-gated K channel from rat atrium, KGA/GIRK1, was expressed in Xenopus oocytes with various receptors and G proteins. The beta 2-adrenergic receptor (beta 2AR), a Gs-linked receptor, activated large KGA currents when the alpha subunit, G alpha s, was also overexpressed. Although G alpha s augmented the coupling between beta 2AR and KGA, G alpha s also inhibited the basal, agonist-independent activity of KGA. KGA currents stimulated via beta 2AR activated, deactivated, and desensitized more slowly than currents stimulated via Gi/Go-linked receptors. There was partial occlusion between currents stimulated via beta 2AR and the m2 muscarinic receptor (a Gi/Go-linked receptor), indicating some convergence in the mechanism of activation by these two receptors. Although stimulation of beta 2AR also activates adenylyl cyclase and protein kinase A, activation of KGA via beta 2AR is not mediated by this second messenger pathway, because direct elevation of intracellular cAMP levels had no effect on KGA currents. Experiments with other coexpressed G protein alpha and beta gamma subunits showed that (a) a constitutively active G alpha s mutant did not suppress basal KGA currents and was only partially as effective as wild type G alpha s in coupling beta 2AR to KGA, and (b) beta gamma subunits increased basal KGA currents. These results reinforce present concepts that beta gamma subunits activate KGA, and also suggest that beta gamma subunits may provide a link between KGA and receptors not previously known to couple to inward rectifiers.

scholarly journals Effects of σ ligands on the nociceptin/orphanin FQ receptor co-expressed with the G-protein-activated K+ channel in Xenopus oocytes

1997 ◽  
Vol 120 (6) ◽  
pp. 986-987 ◽  
Author(s):  
Toru Kobayashi ◽  
Kazutaka Ikeda ◽  
Shunji Togashi ◽  
Noboru Itoh ◽  
Toshiro Kumanishi
Keyword(s):  
G Protein ◽  
Xenopus Oocytes ◽  
K Channel ◽  
Orphanin Fq

Effects of ginsenoside on G protein-coupled inwardly rectifying K+ channel activity expressed in Xenopus oocytes

2003 ◽  
Vol 468 (2) ◽  
pp. 83-92 ◽  
Author(s):  
Seok Choi ◽  
Jun-Ho Lee ◽  
Yang In Kim ◽  
Man-Jong Kang ◽  
Hyewon Rhim ◽  
...  
Keyword(s):  
G Protein ◽  
Xenopus Oocytes ◽  
K Channel ◽  
Channel Activity ◽  
Inwardly Rectifying ◽  
G Protein Coupled

Activation by adrenaline of a low-conductance G protein-dependent K+ channel in mouse pancreatic B cells

Nature ◽  
1991 ◽  
Vol 349 (6304) ◽  
pp. 77-79 ◽  
Author(s):  
Patrik Rorsman ◽  
Krister Bokvist ◽  
Carina Ämmälä ◽  
Per Arkhammar ◽  
Per-Olof Berggren ◽  
...  
Keyword(s):  
B Cells ◽  
G Protein ◽  
K Channel ◽  
Pancreatic B Cells
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